Editing Diffuse axonal injury (section)

===Calcium influx===
While sometimes only the cytoskeleton is disturbed, frequently disruption of the [[axolemma]] occurs as well, causing the influx of [[calcium|Ca<sup>2+</sup>]] ions into the cell and unleashing a variety of degradational processes.<ref name="Lopachin"/><ref name="Povlishock">{{cite book | author = Povlishock JT, Pettus EH | chapter = Traumatically Induced Axonal Damage: Evidence for Enduring Changes in Axolemmal Permeability with Associated Cytoskeletal Change | year = 1996 | title = Mechanisms of Secondary Brain Damage in Cerebral Ischemia and Trauma | journal = Acta Neurochirurgica. Supplement | volume = 66 | pages = 81–86 | doi = 10.1007/978-3-7091-9465-2_15 | pmid = 8780803 | isbn = 978-3-7091-9467-6 }}</ref> An increase in Ca<sup>2+</sup> and [[sodium|Na<sup>+</sup>]] levels and a drop in [[potassium|K<sup>+</sup>]] levels are found within the axon immediately after injury.<ref name="Wolf"/><ref name="Lopachin"/> Possible routes of Ca<sup>2+</sup> entry include [[sodium ion channel|sodium channel]]s, [[membrane pore|pore]]s formed in the membrane during stretch, and failure of [[ATP-dependent transporter]]s due to mechanical blockage or lack of available metabolic energy.<ref name="Wolf"/> High levels of intracellular Ca<sup>2+</sup>, the major cause of post-injury cell damage,<ref name="zhou">{{cite journal | vauthors = Zhou F, Xiang Z, Feng WX, Zhen LX | year = 2001 | title = Neuronal free Ca<sup>2+</sup> and BBB permeability and ultrastructure in head injury with secondary insult | journal = Journal of Clinical Neuroscience | volume = 8 | issue = 6| pages = 561–563 | pmid = 11683606 | doi = 10.1054/jocn.2001.0980 | s2cid = 43789581 }}</ref> destroy mitochondria,<ref name="Smith"/> and trigger [[phospholipase]]s and proteolytic enzymes that damage Na+ channels and degrade or alter the cytoskeleton and the [[axoplasm]].<ref name="Castillo">{{cite journal | author = Castillo MR, Babson JR | year = 1998 | title = Ca<sup>2+</sup>-dependent mechanisms of cell injury in cultured cortical neurons | journal = Neuroscience | volume = 86 | issue = 4| pages = 1133–1144 | pmid = 9697120 | doi = 10.1016/s0306-4522(98)00070-0 | s2cid = 54228571 }}</ref><ref name="Lopachin"/> Excess Ca<sup>2+</sup> can also lead to damage to the [[blood–brain barrier]] and swelling of the brain.<ref name="zhou"/>

One of the proteins activated by the presence of calcium in the cell is [[calpain]], a Ca<sup>2+</sup>-dependent non-[[lysosome|lysosomal]] [[protease]].<ref name="Castillo"/> About 15 minutes to half an hour after the onset of injury, a process called calpain-mediated spectrin proteolysis, or CMSP, begins to occur.<ref name="Büki">{{cite journal | vauthors = Büki A, Okonkwo DO, Wang KK, Povlishock JT | title = Cytochrome c release and caspase activation in traumatic axonal injury | journal = The Journal of Neuroscience | volume = 20 | issue = 8 | pages = 2825–34 | date = April 2000 | pmid = 10751434 | pmc = 6772193 | doi = 10.1523/JNEUROSCI.20-08-02825.2000 | department = primary }}</ref> Calpain breaks down a molecule called [[spectrin]], which holds the membrane onto the cytoskeleton, causing the formation of [[bleb (cell biology)|bleb]]s and the breakdown of the cytoskeleton and the membrane, and ultimately the death of the cell.<ref name="Castillo"/><ref name="Büki"/> Other molecules that can be degraded by calpains are [[microtubule]] subunits, [[microtubule-associated protein]]s, and [[neurofilament]]s.<ref name="Castillo"/>

Generally occurring one to six hours into the process of post-stretch injury, the presence of calcium in the cell initiates the [[caspase]] cascade, a process in cell injury that usually leads to [[apoptosis]], or "programmed cell death".<ref name="Büki"/>

[[Mitochondria]], [[dendrite]]s, and parts of the cytoskeleton damaged in the injury have a limited ability to heal and regenerate, a process which occurs over two or more weeks.<ref name="Corbo">{{cite journal | author = Corbo J, Tripathi P | year = 2004 | title = Delayed presentation of diffuse axonal injury: A case report | journal = Trauma | volume = 44 | issue = 1| pages = 57–60 | pmid = 15226709 | doi = 10.1016/j.annemergmed.2003.11.010 }}</ref> After the injury, [[astrocyte]]s can shrink, causing parts of the brain to atrophy.<ref name="Wasserman"/>